SAXS and X-ray crystallography suggest an unfolding model for the GDP/GTP conformational switch of the small GTPase Arf6. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Molecular Biology Année : 2010

SAXS and X-ray crystallography suggest an unfolding model for the GDP/GTP conformational switch of the small GTPase Arf6.

Valérie Biou
Kaheina Aizel
  • Fonction : Auteur
Pierre Roblin
  • Fonction : Auteur
Aurélien Thureau
Eric Jacquet
Sebastian Hansson
  • Fonction : Auteur
Bernard Guibert
  • Fonction : Auteur
Mahel Zeghouf
Javier Perez
  • Fonction : Auteur
Jacqueline Cherfils
  • Fonction : Auteur

Résumé

The small GTPases Arf1 and Arf6 have nonoverlapping functions in cellular traffic despite their very high sequence and structural resemblance. Notably, the exquisite isoform specificity of their guanine nucleotide exchange factors and their distinctive sensitivity to the drug brefeldin A cannot be explained by any straightforward structural model. Here we integrated structural and spectroscopic methods to address this issue using Δ13Arf6-GDP, a truncated mutant that mimics membrane-bound Arf6-GDP. The crystal structure of Δ13Arf6-GDP reveals an unprecedented unfolding of the GTPase core β-strands, which is fully accounted for by small-angle X-ray scattering data in solution and by ab initio three-dimensional envelope calculation. NMR chemical shifts identify this structural disorder in Δ13Arf6-GDP, but not in the closely related Δ17Arf1-GDP, which is consistent with their comparative thermodynamic and hydrodynamic analyses. Taken together, these experiments suggest an unfolding model for the nucleotide switch of Arf6 and shed new light on its biochemical differences with Arf1.

Domaines

Chimie organique

Dates et versions

hal-00534228 , version 1 (09-11-2010)

Identifiants

Citer

Valérie Biou, Kaheina Aizel, Pierre Roblin, Aurélien Thureau, Eric Jacquet, et al.. SAXS and X-ray crystallography suggest an unfolding model for the GDP/GTP conformational switch of the small GTPase Arf6.. Journal of Molecular Biology, 2010, 402 (4), pp.696-707. ⟨10.1016/j.jmb.2010.08.002⟩. ⟨hal-00534228⟩
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